{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T02:10:11Z","timestamp":1780452611780,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T00:00:00Z","timestamp":1575504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Many anti-obesity chemicals have been withdrawn from the market due to serious adverse reactions, and the researchers have turned their attention to low-toxic natural products. Previous studies have demonstrated that chitosan (CTS) and chitosan oligosaccharide (COS) were low-toxic natural products for the use of weight loss. However, it is still unclear whether CTS and COS have positive effects on the thermogenesis. In this study, CTS and COS significantly reduced the weight gain of rats without affecting food intake and effectively inhibited adipose tissue hypertrophy and hyperplasia. Consistently, CTS and COS significantly increased the thermogenic capacity of obese rats induced by high-fat diet (HFD) and increased the expression of browning genes and proteins (UCP1, PGC1\u03b1, PRMD16, and ATF2) in white adipose tissue (WAT) and brown adipose tissue (BAT). In vitro, COS inhibited the formation of mature adipocytes and increased the expression of browning genes. In conclusion, COS and CTS was used to explore the function and mechanism on thermogenesis, and CTS and COS can increase the browning of WAT and the thermogenesis of BAT to inhibit obesity. This effect may be achieved by promoting the expression of browning and thermogenic genes, providing new ideas for the utilization of COS and CTS.<\/jats:p>","DOI":"10.3390\/molecules24244455","type":"journal-article","created":{"date-parts":[[2019,12,5]],"date-time":"2019-12-05T11:16:23Z","timestamp":1575544583000},"page":"4455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Beneficial Metabolic Effects of Chitosan and Chitosan Oligosaccharide on Epididymal WAT Browning and Thermogenesis in Obese Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9190-6208","authenticated-orcid":false,"given":"Jin","family":"Wang","sequence":"first","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanping","family":"He","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"},{"name":"Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Guo","sequence":"additional","affiliation":[{"name":"Guangdong Metabolic Diseases Research Centre of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Key Laboratory of Modulating Liver to Treat Hyperlipemia SATCM, Level 3 Laboratory of Lipid Metabolism SATCM, Institute of Chinese Medicinal Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-6620","authenticated-orcid":false,"given":"Zhengquan","family":"Su","sequence":"additional","affiliation":[{"name":"Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1001\/jama.2014.732","article-title":"Prevalence of childhood and adult obesity in the United States, 2011\u20132012","volume":"311","author":"Ogden","year":"2014","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/s13679-018-0300-4","article-title":"Future pharmacotherapy for obesity: New anti-obesity drugs on the horizon","volume":"7","author":"Srivastava","year":"2018","journal-title":"Curr. Obes. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"879.e1-6","DOI":"10.1016\/j.amjmed.2016.02.009","article-title":"FDA-Approved anti-obesity drugs in the United States","volume":"129","author":"Daneschvar","year":"2016","journal-title":"Am. J. Med."},{"key":"ref_4","unstructured":"National Institutes of Health (2019, December 01). LiverTox: Clinical and research information on drug-induced liver injury, Available online: https:\/\/livertox.nlm.nih.gov\/\/Infliximab.htm."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mam.2019.07.003","article-title":"Contribution of brown adipose tissue to human energy metabolism","volume":"68","author":"Marlatt","year":"2019","journal-title":"Mol. Asp. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1056\/NEJMoa0810780","article-title":"Identification and importance of brown adipose tissue in adult humans","volume":"360","author":"Cypess","year":"2009","journal-title":"New Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1146\/annurev-physiol-021113-170252","article-title":"A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis","volume":"76","author":"Kajimura","year":"2014","journal-title":"Annu. Rev. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1096\/fj.00-0536fje","article-title":"Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold","volume":"15","author":"Golozoubova","year":"2001","journal-title":"FASEB J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1152\/physrev.00015.2003","article-title":"Brown adipose tissue: Function and physiological significance","volume":"84","author":"Cannon","year":"2004","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Sharp, L.Z., Shinoda, K., Ohno, H., Scheel, D.W., Tomoda, E., Ruiz, L., Hu, H., Wang, L., Pavlova, Z., and Gilsanz, V. (2012). Human BAT possesses molecular signatures that resemble beige\/brite cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0049452"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S0092-8674(00)81410-5","article-title":"A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis","volume":"92","author":"Puigserver","year":"1998","journal-title":"Cell"},{"key":"ref_12","first-page":"1397","article-title":"Regulation of the brown and white fat gene programs through a PRDM16\/CtBP transcriptional complex","volume":"22","author":"Kajimura","year":"2008","journal-title":"Genome Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.cmet.2013.01.015","article-title":"EBF2 determines and maintains brown adipocyte identity","volume":"17","author":"Rajakumari","year":"2013","journal-title":"Cell Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tem.2015.11.005","article-title":"The Multifaceted Roles of PRDM16: Adipose Biology and Beyond","volume":"27","author":"Chi","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/j.celrep.2017.06.069","article-title":"Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat","volume":"20","author":"Yao","year":"2017","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1016\/j.ijbiomac.2017.04.119","article-title":"Physicochemical properties and characterization of chitosan synthesized from fish scales, crab and shrimp shells","volume":"104","author":"Kumari","year":"2017","journal-title":"Int. J. Boil. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.ijbiomac.2019.01.192","article-title":"Chitosan oligosaccharide (COS): An overview","volume":"129","author":"Naveed","year":"2019","journal-title":"Int. J. Boil. Macromol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.pharmthera.2016.10.013","article-title":"Chitosan oligosaccharide: Biological activities and potential therapeutic applications","volume":"170","author":"Muanprasat","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1021\/bm700453x","article-title":"Chitosan as a Lipid Binder: A Langmuir Monolayer Study of Chitosan\u2212Lipid Interactions","volume":"8","author":"Wydro","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"62","DOI":"10.29219\/fnr.v62.1446","article-title":"Cholesterol-lowering effects and potential mechanisms of chitooligosaccharide capsules in hyperlipidemic rats","volume":"62","author":"Jiang","year":"2018","journal-title":"Food Nutr. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4069","DOI":"10.2147\/IJN.S33830","article-title":"Effects of chitosan and water-soluble chitosan micro- and nanoparticles in obese rats fed a high-fat diet","volume":"7","author":"Zhang","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/CIRCRESAHA.115.306647","article-title":"Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis","volume":"118","author":"Hoeke","year":"2016","journal-title":"Circ. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1096\/fj.201600459rr","article-title":"Rutin ameliorates obesity through brown fat activation","volume":"31","author":"Yuan","year":"2017","journal-title":"FASEB J."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yang, D., Hu, C., Deng, X., Bai, Y., Cao, H., Guo, J., and Su, Z. (2019). Therapeutic Effect of Chitooligosaccharide Tablets on Lipids in High-Fat Diets Induced Hyperlipidemic Rats. Molecules, 24.","DOI":"10.3390\/molecules24030514"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pan, H., Fu, C., Huang, L., Jiang, Y., Deng, X., Guo, J., and Su, Z. (2018). Anti-Obesity Effect of Chitosan Oligosaccharide Capsules (COSCs) in Obese Rats by Ameliorating Leptin Resistance and Adipogenesis. Mar. Drugs, 16.","DOI":"10.3390\/md16060198"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1331658","DOI":"10.1080\/16546628.2017.1331658","article-title":"In vitro inhibition of lipid accumulation induced by oleic acid and in vivo pharmacokinetics of chitosan microspheres (CTMS) and chitosan-capsaicin microspheres (CCMS)","volume":"61","author":"Wu","year":"2017","journal-title":"Food Nutr. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.pharmthera.2016.10.015","article-title":"Obesity: Current and potential pharmacotherapeutics and targets","volume":"170","author":"Narayanaswami","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1097\/01.ogx.0000525900.85600.c2","article-title":"Blocking FSH Induces Thermogenic Adipose Tissue and Reduces Body Fat","volume":"72","author":"Liu","year":"2017","journal-title":"Obstet. Gynecol. Surv."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Figueiredo, P.S., Inada, A.C., Marcelino, G., Cardozo, C.M.L., Freitas, K.D.C., Guimar\u00e3es, R.D.C.A., De Castro, A.P., Nascimento, V.A.D., and Hiane, P.A. (2017). Fatty Acids Consumption: The Role Metabolic Aspects Involved in Obesity and Its Associated Disorders. Nutrients, 9.","DOI":"10.3390\/nu9101158"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Walsh, A.M., Sweeney, T., Bahar, B., and O\u2019Doherty, J.V. (2013). Multi-Functional Roles of Chitosan as a Potential Protective Agent against Obesity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053828"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.phrs.2009.02.004","article-title":"The role of PPAR\u03b1 in lipid metabolism and obesity: Focusing on the effects of estrogen on PPAR\u03b1 actions","volume":"60","author":"Yoon","year":"2009","journal-title":"Pharmacol. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.molcel.2014.12.005","article-title":"Cold\u2013inducible Zfp516 Activates UCP1 Transcription to Promote Browning of White Fat and Development of Brown Fat","volume":"57","author":"Dempersmier","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"514","DOI":"10.2337\/db13-1106","article-title":"Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling","volume":"63","author":"Zhang","year":"2013","journal-title":"Diabetes"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1002\/jcp.25299","article-title":"Cell-Autonomous Brown-Like Adipogenesis of Preadipocytes From Retinoblastoma Haploinsufficient Mice","volume":"231","author":"Petrov","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/2464652","article-title":"Adipocyte DIO2 Expression Increases in Human Obesity but Is Not Related to Systemic Insulin Sensitivity","volume":"2018","author":"Bradley","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.2337\/db15-1423","article-title":"\u03b2-Lapachone Prevents Diet-Induced Obesity by Increasing Energy Expenditure and Stimulating the Browning of White Adipose Tissue via Downregulation of miR-382 Expression","volume":"65","author":"Choi","year":"2016","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/nrm2066","article-title":"Adipocyte differentiation from the inside out","volume":"7","author":"Rosen","year":"2006","journal-title":"Nat. Rev. Mol. Cell Boil."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"577","DOI":"10.2337\/diabetes.53.3.577","article-title":"Mice with targeted disruption of the Dio2 gene have cold-induced overexpression of the uncoupling protein 1 gene but fail to increase brown adipose tissue lipogenesis and adaptive thermogenesis","volume":"53","author":"Christoffolete","year":"2004","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4008","DOI":"10.1210\/EN.2015-1209","article-title":"The glucose sensor ChREBP links de-novo lipogenesis to PPAR\u03b3 activity and adipocyte differentiation","volume":"156","author":"Witte","year":"2015","journal-title":"Endocrinology"},{"key":"ref_40","first-page":"80","article-title":"Chitosan oligosaccharides inhibit adipogenesis in 3T3-L1 adipocytes","volume":"18","author":"Cho","year":"2008","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.carbpol.2017.12.067","article-title":"Chitooligosaccharides and their biological activities: A comprehensive review","volume":"184","author":"Liaqat","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1021\/jf4040628","article-title":"Antiobese Effects of Capsaicin\u2013Chitosan Microsphere (CCMS) in Obese Rats Induced by High Fat Diet","volume":"62","author":"Tan","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Scheele, C., and Wolfrum, C. (2019). Brown adipose cross talk in tissue plasticity and human metabolism. Endocr. Rev.","DOI":"10.1210\/endrev\/bnz007"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/nrendo.2016.136","article-title":"Brown adipose tissue as a secretory organ","volume":"13","author":"Villarroya","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Sun, N.-N., Wu, T.-Y., and Chau, C.-F. (2016). Natural Dietary and Herbal Products in Anti-Obesity Treatment. Molecules, 21.","DOI":"10.3390\/molecules21101351"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.3390\/md13031133","article-title":"Chitin and Chitosan Preparation from Marine Sources. Structure, Properties and Applications","volume":"13","author":"Younes","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Sharif, R., Mujtaba, M., Rahman, M.U., Shalmani, A., Ahmad, H., Anwar, T., Tianchan, D., and Wang, X. (2018). The Multifunctional Role of Chitosan in Horticultural Crops; A Review. Molecules, 23.","DOI":"10.3390\/molecules23040872"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2732","DOI":"10.3390\/md13052732","article-title":"Anti-Obese Effect of Glucosamine and Chitosan Oligosaccharide in High-Fat Diet-Induced Obese Rats","volume":"13","author":"Huang","year":"2015","journal-title":"Mar. Drugs"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:40:26Z","timestamp":1760190026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/24\/4455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,5]]},"references-count":48,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["molecules24244455"],"URL":"https:\/\/doi.org\/10.3390\/molecules24244455","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,5]]}}}